Cited by 260Cytokine Signaling Pathways and InteractionsPsoriasis: Treatment and PathogenesisT-cell and B-cell Immunology

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Identification, Cloning, and Characterization of a Novel Soluble Receptor That Binds IL-22 and Neutralizes Its Activity

Kotenko, Sergei V, Izotova, Lara S, Mirochnitchenko, Olga V, Esterova, Elena, Dickensheets, Harold, Donnelly, Raymond P, Pestka, Sidney·2001·The Journal of Immunology

DOI 10.4049/jimmunol.166.12.7096

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Abstract

With the use of a partial sequence of the human genome, we identified a gene encoding a novel soluble receptor belonging to the class II cytokine receptor family. This gene is positioned on chromosome 6 in the vicinity of the IFNGR1 gene in a head-to-tail orientation. The gene consists of six exons and encodes a 231-aa protein with a 21-aa leader sequence. The secreted mature protein demonstrates 34% amino acid identity to the extracellular domain of the IL-22R1 chain. Cross-linking experiments demonstrate that the protein binds IL-22 and prevents binding of IL-22 to the functional cell surface IL-22R complex, which consists of two subunits, the IL-22R1 and the IL-10R2c chains. Moreover, this soluble receptor, designated IL-22-binding protein (BP), is capable of neutralizing IL-22 activity. In the presence of the IL-22BP, IL-22 is unable to induce Stat activation in IL-22-responsive human lung carcinoma A549 cells. IL-22BP also blocked induction of the suppressors of cytokine signaling-3 (SOCS-3) gene expression by IL-22 in HepG2 cells. To further evaluate IL-22BP action, we used hamster cells expressing a modified IL-22R complex consisting of the intact IL-10R2c and the chimeric IL-22R1/γR1 receptor in which the IL-22R1 intracellular domain was replaced with the IFN-γR1 intracellular domain. In these cells, IL-22 activates biological activities specific for IFN-γ, such as up-regulation of MHC class I Ag expression. The addition of IL-22BP neutralizes the ability of IL-22 to induce Stat activation and MHC class I Ag expression in these cells. Thus, the soluble receptor designated IL-22BP inhibits IL-22 activity by binding IL-22 and blocking its interaction with the cell surface IL-22R complex.

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Authors: Kotenko, S. V., Izotova, L. S., Mirochnitchenko, O. V., Esterova, E., Dickensheets, H., Donnelly, R. P., & Pestka, S.
Affiliations: Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry, Robert Wood Johnson Medical School , Piscataway, NJ 08854
Center for Biologics Evaluation and Research (US)
ORCID: Kotenko, Sergei V
Donnelly, Raymond P
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2001-06
Volume: 166
Issue: 12
Pages: 7096-7103
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.166.12.7096
OpenAlex: W1938903801
Cited by: 260
References: 32
Citations by year: 2026: 1 · 2025: 3 · 2024: 10 · 2023: 12 · 2022: 6 · 2021: 15 · 2020: 16 · 2019: 10 · 2018: 19 · 2017: 11 · 2016: 14 · 2015: 12 · 2014: 11 · 2013: 12 · 2012: 10
FWCI: 7.06
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (1P30-CA72720, R01 CA-46465, R01CA046465, P30CA072720)
National Institute of Allergy and Infectious Diseases (R01-AI43369, R01-AI36450, R01AI043369, R01AI036450)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: soluble receptor, IL-22, STAT activation, SOCS3, MHC class I expression, IFNGR1, chromosome 6, gene cloning
MeSH terms: Interleukin-22, Amino Acid Sequence, Animals, Base Sequence, Binding, Competitive, Carrier Proteins, Cloning, Molecular, Cricetinae, Humans, Interleukins, Ligands, Molecular Sequence Data, Receptors, Cell Surface, Solubility, Tumor Cells, Cultured, CHO Cells, DNA, Complementary, Receptors, Interleukin, COS Cells

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Identification, Cloning, and Characterization of a Novel Soluble Receptor That Binds IL-22 and Neutralizes Its Activity

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